A sequential study of the time-dependent effects of the selective type A monoamine oxidase-inhibiting antidepressant clorgyline has begun in rodents. A change in presynaptic release mechanisms has been observed to develop during chronic clorgyline treatment. This likely adaptation to increased norepinephrine levels following sustained MAO inhibitor treatment is at least in part responsible for post-synaptic adaptive changes we have observed such as Beta-adrenergic receptor down-regulation. Some evidence that these biochemical changes are likely to be of physiological and pharmacological importance for our understanding of the side effects and efficacy of antidepressants comes from recently-collected data indicating that self-stimulation behavior in rodents appears to be correlated with these changes.